In medical practice, in the development of new drugs and in skin testing procedures it is important to determine physiological responses such as the degree of vasodilatation or vasoconstriction in the microcirculation following application of a vasoactive drug directly in contact with the skin or administrated by other routes. A suitable way of transdermal drug administration is by means of iontophoresis in order to support penetration of charged drug molecules through the epidermal layer or by topical application of the drug or agent.
Although the reddening of the skin generally can be seen by the naked eye, a more objective method is generally used in the medical setup. Laser Doppler perfusion imaging (Wårdell K., Jakobsson, A. J. and Nilsson, G. E. Laser Doppler Perfusion Imaging by Dynamic Light Scattering. IEEE Trans BME, Vol 40, No. 4, 309-316, 1993.) is a method that by sequentially scanning the tissue surface of interest, gives a quantitative measure of the increase in blood perfusion and thus a measure of the effect on the microvasculature of the vasoactive drug under study. Alternatively a single point laser Doppler perfusion monitor may be used for monitoring the tissue blood perfusion. Using the combined setup of iontophoresis and laser Doppler perfusion imaging, several critical parameters of iontophoresis—including current strength, effect of inflammatory processes, and vasoactive drug dosage (Droog E. J. and Sjöberg F. Nonspecific vasodilatation during transepidermal iontophoresis—the effect of voltage over the skin, Microvascular Research, 65(2003) 172-178; Droog, E. G., Henricsson, J., Nilsson, G. E. and Sjöberg, F. A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimizes non-specific vasodilatory effects, Microvascular Research, 67 (2004) 197-220)—have been studied and optimized. In clinical settings this combined technology of iontophoresis and laser Doppler perfusion imaging has been used in studies of the response to transepidermally applied vasoactive drugs in patients with diabetes (Morris, S. J., Shore, A. C. and Tooke, J. E. Responses of the skin microcirculation to acetylcholine and sodium nitroprusside in patients NIDDM, Diabetologica 38, 1337-1344, 1995) and in patients with Alzheimer's disease (Algotsson, A., Nordberg, A, Almkvist, O. and Winblad, B. Skin vessel reactivity is impaired in Alzheimer's disease. Neurobiol Aging. 1995 July-August; 16(4):577-82).
Laser Doppler perfusion imaging (and monitoring) is, however, a technology not very well suited for applications in primary care or in the office of the general practitioner, because of high cost and to some extent cumbersome handling and image interpretation. Besides, laser Doppler perfusion imaging (and monitoring) gives a representation of the tissue blood perfusion rather than the vasodilatation or vasoconstriction of the microvascular bed as a response to the vasoactive agent.
A companion technology entitled Orthogonal Polarization Spectroscopy using a selected illumination band of wavelengths has earlier been used in microscopes in an attempt to visualize the detailed architecture of the smallest vessels of the microcirculation (Uhl, E., Lehmberg, J., Steiger, H. J. and Messmer, K Intraoperative detection of early microvasospasm in patients with subarachnoid hemorrhage by using orthogonal polarization spectral imaging, Neurosurgery, June 2003 52(6) 1307-15). The high degree of magnification required, however, makes this technology difficult to use in primary care and in the general practitioner's office, because of the inevitable relative movement between the microscope and the object. Besides, the end result is in best case a structural image of the minute vessels in a small area and gives no direct information about the average vasodilatation of a more extensive skin site.
Obviously, there is demand for a complementary technology, that can be applied in for example test laboratories for skin care product evaluation and in diabetes clinics and primary care at low costs to identify patients, who are at risk of acquiring more profound complications from diseases known to cause impaired circulation, for a preventing regimen or therapy.